ORIGINAL RESEARCH ARTICLE Altered immunoreactive levels of G proteins in peripheral mononuclear cells of patients with anorexia nervosa and bulimia nervosa P Monteleone, A Di Lieto, V Martiadis, M Pannuto and M Maj Department of Psychiatry, University of Naples S.U.N., Naples, Italy Alterations of cellular G proteins have been implicated in the pathophysiology of some psychiatric disorders. So far, no study assessed G protein function in anorexia nervosa (AN) and bulimia nervosa (BN). Therefore, we measured immunoreactive levels of G as ,G ai ,G aq/11 and G b protein subunits in mononuclear leukocytes of 71 drug-free women, including 25 subjects with AN, 26 individuals with BN and 20 healthy controls. As compared to healthy women, anorexic patients exhibited significantly increased levels of G ai and G b proteins, while bulimic patients had significantly increased levels of G as ,G ai and G b proteins. Immunoreactive levels of peripheral G protein subunits were not significantly correlated with demographic or nutritional parameters. These findings, although obtained in peripheral blood cells, may suggest a derangement of G protein-mediated signal transduction in the pathophysiology of eating disorders. Molecular Psychiatry (2003) 8, 680–684. doi:10.1038/sj.mp.4001304 Keywords: anorexia nervosa; bulimia nervosa; eating disorders; G proteins; signal transduction Abnormalities in signal transduction pathways have been demonstrated in a variety of human diseases. 1,2 Part of these alterations consists of dysfunctions of guanine nucleotide binding proteins (G proteins) that are key elements in the transmission of signal from membrane receptors to effector proteins. Heterotrimeric G proteins are localized in the inner surface of the plasma membrane and consist of an a subunit, which binds and hydrolyses guanine triphosphate, and b and g subunits, which form a tightly but noncovalently linked dimer. 1 The family of G proteins is a crucial point of convergence in the transmission of signals from a variety of hormone and neurotransmitter membrane receptors to a series of downstream intracellular events. It has been esti- mated that about 80% of all known hormones and neurotransmitters elicit cellular response through G proteins coupled to a variety of intracellular second messengers, effector enzymes and ionic channels. 1 In the central nervous system (CNS), the ability of many G proteins to interact with multiple receptors pro- vides an efficient mechanism for the neuron to organize, integrate and amplify signals from a large number of neurotransmitter pathways. Therefore, in view of their critical role in signal processing, it seems likely that both qualitative and quantitative dysfunctions of G proteins may lead to altered CNS functions and disturbed behaviours. Recently, evidence has been provided that altera- tions in either the levels and/or the function of the a subunit of the stimulatory G protein (G as ) occur in peripheral cells from subjects with bipolar disor- ders. 3–7 Similarly, modifications in the various sub- units of G proteins have been demonstrated in both the periphery and the CNS of schizophrenic patients, 8–10 whereas no change has been detected in patients with panic disorder. 11 An increasing body of evidence also suggests that psychotropic drugs, upon chronic administration, may exert effects at postreceptor sites, in particular, at the level of G proteins. 2 To the best of our knowledge, no study explored so far the functional status of the signal-transducing G proteins in patients with anorexia nervosa (AN) or bulimia nervosa (BN). These disorders are character- ized by multiple neurotransmitter and neurohormone alterations, concomitant depressive and anxious symptoms, and several malnutrition-induced physio- logical aberrations. Furthermore, it is known that most of the neurotransmitters and neuropeptides implicated in the modulation of eating behaviour and energy homeostasis act through G protein- coupled membrane receptors. Therefore, the assess- ment of G proteins in patients with eating disorders seems to be of great interest. Received 22 July 2002; revised 11 September 2002; accepted 8 November 2002 Correspondence: Dr P Monteleone, MD, Department of Psychiatry, University of Naples S.U.N., Largo Madonna delle Grazie, 80138 Naples, Italy. E-mail: monteri@tin.it Molecular Psychiatry (2003) 8, 680–684 & 2003 Nature Publishing Group All rights reserved 1359-4184/03 $25.00 www.nature.com/mp